Clinical Trials /

A Study Evaluating the Safety of Cal-1 (LVsh5/C46) Drug Product in HIV-1 Infected Patient With High Risk Lymphoma

NCT03593187

Description:

The purpose of this study is to evaluate the safety and the feasibility, and the success of engraftment of the introduction of Cal-1 gene-transduced haematopoietic cell populations (Ttn and HSPCtn) in patients with HIV-1-related high-risk lymphoma.

Related Conditions:
  • Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety of Cal-1 (LVsh5/C46) Drug Product in HIV-1 Infected Patient With High Risk Lymphoma
  • Official Title: A Phase I/II Study of the Safety of CD34+ Haematopoietic Stem/Progenitor Cells and CD4+ T Lymphocytes Transduced With LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct, in HIV-1 Infected Patients With High-risk Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: P 141004
  • SECONDARY ID: 2015-004453-41
  • NCT ID: NCT03593187

Conditions

  • HIV-1 Infection

Interventions

DrugSynonymsArms
Cal-1 (LVsh5/C46) drug productCal-1( LVsh5/C46) drug product

Purpose

The purpose of this study is to evaluate the safety and the feasibility, and the success of engraftment of the introduction of Cal-1 gene-transduced haematopoietic cell populations (Ttn and HSPCtn) in patients with HIV-1-related high-risk lymphoma.

Detailed Description

      not provided
    

Trial Arms

NameTypeDescriptionInterventions
Cal-1( LVsh5/C46) drug productExperimental
  • Cal-1 (LVsh5/C46) drug product

Eligibility Criteria

        Inclusion Criteria:

        Eligible subjects will undergo screening assessments at three time points:

          -  Screening 1 at the beginning of chemotherapy,

          -  Screening 2 (first "check-point") after the harvest for CD34,

          -  Screening 3 (second "check-point") before the ASCT procedure. Potential subjects must
             satisfy all of the inclusion criteria to be enrolled in the study and proceed with the
             first apheresis (day -39).

        In-A. Prior to any study-related procedures, signed informed consent indicating that they
        understand the purpose, risks and procedures required for the study and are willing to
        participate in the study In-B. Individuals aged 18 to 60 years of age (inclusive) at time
        of consent In-C. Women with child-bearing potential must be on adequate effective
        contraception (continuous progestative contraception) In-D. Documented HIV-1 infection at
        or before the time of lymphoma diagnosis In-E. Treatment with antiretroviral agents
        (excluding NNRTI) introduced or optimized at the time of screening

        In-F. Biopsy-proven lymphoma meeting one of the following criteria:

          1. 1. Intermediate- or high-grade B-cell non-Hodgkin lymphoma, meeting 1 of the following
             criteria:

               -  in first complete remission with high-risk features such as T-cell lymphoma and
                  plasmablastic lymphoma (after multidisciplinary consultation regarding the
                  indication of ASCT in this context). The decision of ASCT is independent of the
                  present clinical trial.

               -  in partial remission

               -  relapsed after initial complete remission

               -  failed induction therapy but responds to salvage therapy (i.e., chemosensitive
                  disease)

          2. Hodgkin lymphoma, meeting 1 of the following criteria:

               -  in first or greater relapse after initial complete remission

               -  in partial remission

               -  failed induction therapy but responds to salvage therapy (i.e. chemosensitive
                  disease)

          3. High-risk lymphoma requiring a treatment with combined chemotherapy and autologous
             stem cell transplantation (ASCT)

        Exclusion Criteria:

        Ex-A. -Left ventricular ejection fraction <50% at Screening 1:

        Ex-B. Abnormal biochemistry at Screening 1:

        Alanine and/or aspartate aminotransferase (ALT/AST) >10 x upper limit of normal (ULN) Total
        bilirubin > 2.5 x ULN Creatinine clearance <60ml/min Ex-C. Severe coagulopathy Ex-D.
        Prothombin time > 2x ULN Ex-E. Evidence of co-infection with hepatitis B virus (HBsAg+),
        hepatitis C virus, West Nile Virus, or Human T-lymphotropic virus (HTLV-1) as detected at
        Screening 1 Ex-F. Stay in West Nile Virus endemic area less than 6 weeks prior to CD34+
        collection Ex-G. Evidence of non-treated opportunistic infection during the pre-infusion
        period Ex-H. Evidence of not-treated CNS involvement of lymphoma at Screening 1 Ex-I.
        Isolated CNS relapse of the lymphoma without other evidence of active disease at Screening
        1 Ex-J. Known hypersensitivity to G-CSF (Neupogen™) or plerixafor (Mozobil™) Ex-K. Evidence
        of uncontrolled HIV-1 viremia at screening 2 and/or 3 (plasma HIV-1 RNA ≥ 1.000 copies/ml
        confirmed in 2 successive blood samples) Ex-L. Evidence of chemoresistant lymphoma at
        screening 2 Ex-M. Any contra-indication to ASCT at any time during the pre-infusion period
        Ex-N. Participation in any study involving any investigational drug or medical device
        within 3 months prior to Screening 1 Ex-O. Receipt of a vaccine for HIV-1 or any gene
        transfer product at any time Ex-P. Subjects who will not accept transfusions of blood
        products Ex-Q. Pregnant or breast-feeding woman at any time Ex-R. Woman of child-bearing
        potential not under adequate contraceptive protection at any time Ex-S. Inability to
        understand and provide informed consent Psychological or psychiatric disability thought to
        be clinically significant in the opinion of the investigator
      
Maximum Eligible Age:60 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse event post transplant
Time Frame:24 months post-transplant
Safety Issue:
Description:to evaluate the procedure safety

Secondary Outcome Measures

Measure:Overall survival
Time Frame:24 months post-transplant
Safety Issue:
Description:
Measure:Absence of detection of vector-derived Replication competent lentivirus (RCL)
Time Frame:24 months post-transplant
Safety Issue:
Description:
Measure:Frequency and severity of clinical adverse events
Time Frame:24 months post-transplant
Safety Issue:
Description:as assessed by the United States national Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Measure:Absence of tropism shift from R5 to dual/mixed or X4 at any point after Day 0
Time Frame:24 months post-transplant
Safety Issue:
Description:
Measure:Quantify gene transfer efficiency and expression
Time Frame:24 months post-transplant
Safety Issue:
Description:extent of HSPCtn and Ttn survival as measured by Cal-1 marking and expression in peripheral blood
Measure:Time to restart antiretroviral therapy
Time Frame:24 months post-transplant
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Assistance Publique - Hôpitaux de Paris

Trial Keywords

  • HIV-1
  • Lymphoma
  • Gene therapy

Last Updated

January 17, 2020